Spirituality has been found to have some protective effect against pain experiences in cancer patients, but its role in alleviating total pain is not well understood. Intervening factors such as meaning in life and coping with pain also have not been closely examined in cancer patients. This study investigated the serial mediating effects of meaning in life and pain coping on the relationship between spirituality-conceptualized in terms of religious attitudes, ethical sensitivity, and inner harmony-and total pain, which encompasses physical, psychological, social, and spiritual struggles among post-treatment cancer patients. A total of 285 patients (52.8% female) who had completed their treatment filled in self-report measures of spirituality, meaning in life, pain coping strategies, and total pain. Inner harmony was negatively related to physical pain, psychological pain, social pain, and spiritual pain. In contrast, religiosity was not related to any dimensions of total pain. Yet, religiosity was positively related to the use of some pain coping strategies, including diverting attention, reinterpreting pain sensations, ignoring sensations, praying and hoping, and increasing activities. The main indirect effect of spirituality as a latent variable on total pain occurred through presence of meaning, search for meaning, and three pain coping strategies: diverting attention, catastrophizing, and ignoring sensations. The findings indicate a serial mediation model in which the relationship of spirituality as a latent construct with total pain is mediated through two types of mediators (meaning in life and pain coping). Therefore, religiosity, ethical sensitivity and inner harmony taken together as a latent variable could be associated with lower pain due to finding meaning in life, avoiding unreflective coping, and diverting attention from aversive experience of pain.